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Bovine leukemia virus (BLV) main host cells are B lymphocytes. Infected animals can be classified into high or low proviral load (HPL or LPL respectively), regarding the number of proviral copies infected lymphocytes they carry. After infection, there is an overexpression of several cytokines, particularly TNF-α, which has a delicate regulation mediated by receptors TNFRI and TNFRII; the first one involved with apoptosis, while the other stimulates cell proliferation. The study aimed to quantify TNF-α and its receptors mRNA expression, and in which extent in vitro proliferation was affected, in peripheral blood mononuclear cells (PBMC) from BLV-infected animals with different proviral loads, after the addition or not of synthetic TNF-α (rTNF-α) for 48 h. PBMC from BLV-infected animals showed spontaneous proliferation after 48 h in culture but did not show changes in proliferation rates after 48 h incubation in the presence of the rTNF-α. TNF-α mRNA expression after 48 h culture without exogenous stimulation was significantly lower, regardless of the proviral load of the donor, compared to non-infected animals. In the LPL animals, the expression of TNF-α mRNA was significantly lower with respect to the control group while the expression of TNFRI mRNA was significantly increased. The HPL animals showed a significant decrease in the expression of TNF-α and TNFRII mRNA respect to the control group. After 48 h incubation with rTNF-α, PBMC from infected animals had different responses: TNF-α and TNFRI mRNA expression was reduced in PBMC from the LPL group compared to the BLV negative group, but no differences were observed in PBMC from the HPL group. TNFRII mRNA expression showed no differences between HPL, LPL, and BLV negative groups, though HPL animals expressed 10.35 times more TNFRI mRNA than LPL. These results support the hypothesis that LPL animals, when faced with viral reactivation, present a pro-apoptotic and anti-proliferative state. However, complementary studies are needed to explain the influence of TNFRII on the development of the HLP profile. On the other hand, exogenous stimulation studies reinforce the hypothesis that BLV infection compromises the immune response of the animals., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

In hypertension induced by angiotensin II (AngII) administration with high salt (HS) intake, intrarenal angiotensinogen (AGT) and tumor necrosis factor-alpha (TNF-α) levels increase. However, TNF-α has been shown to suppress AGT formation in cultured renal proximal tubular cells. We examined the hypothesis that elevated AngII levels during HS intake reduces TNF-α receptor type 1 (TNFR1) activity in the kidneys, thus facilitating increased intrarenal AGT formation. The responses to HS diet (4% NaCl) with chronic infusion of AngII (25 ng/min) via implanted minipump for 4 weeks were assessed in wild-type (WT) and knockout (KO) mice lacking TNFR1 or TNFR2 receptors. Blood pressure was measured by tail-cuff plethysmography, and 24-h urine samples were collected using metabolic cages prior to start (0 day) and at the end of 2nd and 4th week periods. The urinary excretion rate of AGT (uAGT; marker for intrarenal AGT) was measured using ELISA. HS +AngII treatment for 4 weeks increased mean arterial pressure (MAP) in all strains of mice. However, the increase in MAP in TNFR1KO (77 ± 2 to 115 ± 3 mmHg; n = 7) was significantly greater (p < 0.01) than in WT (76 ± 1 to 102 ± 2 mmHg; n = 7) or in TNFR2KO (78 ± 2 to 99 ± 5 mmHg; n = 6). The increase in uAGT at 4th week was also greater (p < 0.05) in TNFR1KO mice (6 ± 2 to 167 ± 75 ng/24 h) than that in WT (6 ± 3 to 46 ± 16 ng/24 h) or in TNFR2KO mice (8 ± 7 to 65 ± 44 ng/24 h). The results indicate that TNFR1 exerts a protective role by mitigating intrarenal AGT formation induced by elevated AngII and HS intake., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Intravenous infusion of relatively higher doses of angiotensin II (AngII) elicits natriuresis as opposed to its usual anti-natruretic response. As AngII can induce tumor necrosis factor-α (TNFα) production which elicits natriuresis via its action on TNFα receptor type 1 (TNFR1), we hypothesize that the concomitant release of TNFα contributes to the natriuretic response to AngII. Responses to AngII infusion (1 ng min -1  g -1 for 75 min, iv) were evaluated in anesthetized knockout (KO) mice lacking TNFR1 (n = 6) and TNFR2 (TNFα receptor type 2; n = 6) and compared these responses with those in wild type (WT; n = 6) mice. Arterial pressure (AP) was recorded from a cannula placed in the carotid artery. Renal blood flow (RBF) and glomerular filtration rate (GFR) were measured by PAH and inulin clearances, respectively. Urine was collected from a catheter placed in the bladder. AngII caused similar increases (p < 0.05 vs basal values) in AP (WT, 37 ± 5%; TNFR1KO, 35 ± 4%; TNFR2KO, 30 ± 4%) and decreases (p < 0.05) in RBF (WT, -39 ± 5%; TNFR1KO, -28 ± 6%; TNFR2KO, -31 ± 4%) without significant changes in GFR (WT, -17 ± 7%; TNFR1KO, -18 ± 7%; TNFR2KO, -12 ± 7%). However, despite similar changes in AP and renal hemodynamics, AngII induced increases (p < 0.05) in urinary sodium excretion in WT (3916 ± 942%) were less in the KO strains, more or less in TNFR1KO (473 ± 170%) than in TNFR2KO (1176 ± 168%). These data indicate that TNF-α receptors, particularly TNFR1 are involved in the natriuretic response that occur during acute infusion of AngII and thus, plays a protective role in preventing excessive salt retention at clinical conditions associated with elevated AngII level., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

To evaluate the concentration of tumor necrosis factor α (TNF-α) and its soluble receptors (sTNFR I and II) in serum and follicular fluid (FF) at the time of oocyte retrieval and to detect expression of TNF-α and its receptors by luteinized granulosa cells (GCs). In a cross-sectional study and through an in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) program, 81 women undergoing oocyte retrieval were recruited. Serum and FF were obtained from 81 women. GCs were pooled from 20 patients (from six different days of oocyte retrievals, 5-16 follicles per patient). TNF-α and its soluble receptors concentration were determined by enzyme-linked immunosorbent assay and also their expression by immune cytochemistry and reverse-transcription polymerase chain reaction analysis. The median TNF-α concentration in serum was 4.06 pg/ml (interquartile range [IQR], 3.71-6.14) and significantly higher than that in FF with 3.50 pg/ml (IQR, 3.05-5.01), p < 0.001. The sTNFR I and II levels in serum were lower and higher than FF, respectively. The TNF-α levels in serum and FF of good responders were higher than low responders (p = 0.017 and 0.021, respectively). TNF-α cut-off level for low responders versus good responders was 4.174 pg/ml in serum with a pregnancy rate of 25.8% and 40% for below and above of this level, respectively (p = 0.19). For FF, the cut-off value was 3.89 pg/ml. TNF-α and its receptors were expressed by GCs. The presence of TNF-α and its soluble receptors in serum and FF and their expression by GCs suggest an important role for this cytokine in ovarian function., (© 2019 Wiley Periodicals, Inc.)

Background.  During pregnancy, the placenta is inaccessible for diagnosis of placental malaria (PM), but soluble tumor necrosis factor-α receptors (sTNFR) are elevated in the plasma of women with PM. Methods.  In this study, sTNFR-1 and sTNFR-2 were quantified in urine of pregnant and nonpregnant Cameroonian women who were positive or negative for malaria by blood-smear microscopy. Results.  We found that levels of both sTNFR in urine were higher in pregnant compared with nonpregnant women, but malaria-positive pregnant women excreted substantially more sTNFR-1 (P = .005) and sTNFR-2 (P < .001) than malaria-negative pregnant women. The amount of sTNFR-1(rs = 0.784, P < .001) and sTNFR-2 (rs = 0.816, P < .001) in urine correlated with parasitemia, even in afebrile pregnant women. Urine sTNFR-2 predicted maternal malaria with an area under curve of 0.892 (95% confidence interval, .787-.898). At cutoff concentrations of 9.8 ng and 13.6 ng of sTNFR-2 per mL urine, the sensitivity/specificity were 82.6%/87.0% and 78.3%/95.7%, respectively. Conclusions.  The sTNFR-2 in noninvasive urine samples may be useful for diagnosis of malaria during pregnancy.

Background Context: Sciatica is a condition characterized by radicular pain that can be secondary to a lumbar disc herniation (LDH). More than 10% of patients report persistent pain after surgery. The underlying mechanisms of postoperative sciatica remain unclear. There is evidence demonstrating that inflammation plays a role in the pathophysiology of sciatica., Purpose: The study aimed to assess if the expression of tumor necrosis factor (TNF)-α and its receptors (TNFR) was correlated with the severity of pre- and postoperative leg pain in LDH patients who underwent single or multiple decompressive discectomies., Setting: This is an experimental prospective human study of intraoperative intervertebral disc (IVD) samples, as well as a clinical scores evaluation., Methods: We analyzed the mRNA and protein levels of TNF-α, TNFR1, and TNFR2 in IVD biopsies, and correlated them with visual analogue scale (VAS) scores 1 day before surgery to 6 weeks and 6 months postoperatively., Results: We evaluated the correlation between the inflammation in IVD with pre- and postoperative pain scores after discectomy in LDH patients operated for the first time (fLDH, N=12) and for recurrent cases (rLDH, N=8). This analysis showed that TNF-α and TNFR1 mRNA levels were significantly greater in rLDH patients; there was a twofold increase for TNF-α and a 50% increase for TNFR1. Similarly, protein levels in IVD samples positively correlated with postoperative VAS scores, whereas TNFR2 protein levels negatively correlated with postoperative VAS scores., Conclusions: These findings indicate that rLDH patients present higher postoperative VAS scores compared with fLDH patients, and also that these scores are correlated with increased inflammation and may contribute to pain chronicity., (Copyright © 2015 Elsevier Inc. All rights reserved.)